Higher diagnostic value of next-generation sequencing versus culture in periprosthetic joint infection: A systematic review and meta-analysis.

BACKGROUND: The next-generation sequencing (NGS) has developed rapidly in the past decade and is becoming a promising diagnostic tool for periprosthetic infection (PJI). However, its diagnostic value for PJI is still uncertain. The purpose of this systematic review and meta-analysis was to evaluate the diagnostic value of NGS compared to culture. METHODS: In this systematic review and meta-analysis, electronic databases including PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science and clinicaltrials.gov were searched for studies from inception to 12 November 2023. Diagnostic parameters, such as sensitivity, specificity, diagnostic odds ratio and area under the summary receiver-operating characteristic (SROC) curve (AUC), were calculated for the included studies. A systematic review and meta-analysis was performed. RESULTS: A total of 22 studies with 2461 patients were included in our study. The pooled sensitivity, specificity and diagnostic odds ratio of NGS were 87% (95% confidence interval [CI]: 83-90), 94% (95% CI: 91-96) and 111 (95% CI: 70-177), respectively. On the other hand, the pooled sensitivity, specificity and diagnostic odds ratio of culture were 63% (95% CI: 58-67), 98% (95% CI: 96-99) and 93 (95% CI: 40-212), respectively. The SROC curve for NGS and culture showed that the AUCs are 0.96 (95% CI: 0.94-0.98) and 0.82 (95% CI: 0.79-0.86), respectively. CONCLUSION: This systematic review and meta-analysis found NGS had higher sensitivity and diagnostic accuracy but slightly lower specificity than culture. Based on the pooled results, we suggested NGS may have the potential to be a new tool for the diagnosis of PJI. LEVEL OF EVIDENCE: Level IV.

Early surgery within 48 h was associated with reduced perioperative blood loss and red blood cell transfusion requirements in older patients with hip fracture: a retrospective study.

PURPOSE: The aim of this study was to analyze the relationship between the timing of surgery and perioperative blood loss, red blood cell (RBC) transfusion rate, and RBC transfusion volume in older patients with hip fracture. METHODS: From January 2020 to August 2022, this retrospective study enrolled older patients with hip fracture who underwent surgery in our hospital. The demographics, fracture type, type of surgery, time from injury to hospital, timing of surgery, medical history (hypertension, diabetes), duration of surgery, intraoperative blood loss, laboratory tests, and preoperative, postoperative and perioperative RBC transfusion requirements were recorded and analyzed. According to the surgical treatment within 48 h or after 48 h after admission, the patients were divided into early surgery group (ES) and delayed surgery group (DS). RESULTS: A total of 243 older patients with hip fracture were finally included in the study. Among these, 96 patients (39.51%) underwent surgery within 48 h of admission and 147 (60.49%) underwent surgery after this time. Total blood loss (TBL) in the ES group was lower than that in the DS group (576.03 ± 265.57 ml vs 699.26 ± 380.58 ml, P = 0.003). Preoperative RBC transfusion rate, and preoperative and perioperative RBC transfusion volume in the ES group were significantly lower than those in the DS group (15.63% vs 26.53%, P = 0.046; 50.00 ± 128.15 ml vs 117.01 ± 225.85 ml, P = 0.004; 80.21 ± 196.63 ml vs 144.90 ± 253.52 ml, P = 0.027). CONCLUSION: Timing of surgery within 48 h of admission for older patients with hip fracture was associated with reduced the total blood loss and RBC transfusion requirements during the perioperative period.

The neurovascular unit in healthy and injured spinal cord.

The neurovascular unit (NVU) reflects the close temporal and spatial link between neurons and blood vessels. However, the understanding of the NVU in the spinal cord is far from clear and largely based on generalized knowledge obtained from the brain. Herein, we review the present knowledge of the NVU and highlight candidate approaches to investigate the NVU, particularly focusing on the spinal cord. Several unique features maintain the highly regulated microenvironment in the NVU. Autoregulation and neurovascular coupling ensure regional blood flow meets the metabolic demand according to the blood supply or local neural activation. The blood-central nervous system barrier partitions the circulating blood from neural parenchyma and facilitates the selective exchange of substances. Furthermore, we discuss spinal cord injury (SCI) as a common injury from the perspective of NVU dysfunction. Hopefully, this review will help expand the understanding of the NVU in the spinal cord and inspire new insights into SCI.

Pathological hemodynamic changes and leukocyte transmigration disrupt the blood-spinal cord barrier after spinal cord injury.

BACKGROUND: Blood-spinal cord barrier (BSCB) disruption is a key event after spinal cord injury (SCI), which permits unfavorable blood-derived substances to enter the neural tissue and exacerbates secondary injury. However, limited mechanical impact is usually followed by a large-scale BSCB disruption in SCI. How the BSCB disruption is propagated along the spinal cord in the acute period of SCI remains unclear. Thus, strategies for appropriate clinical treatment are lacking. METHODS: A SCI contusion mouse model was established in wild-type and LysM-YFP transgenic mice. In vivo two-photon imaging and complementary studies, including immunostaining, capillary western blotting, and whole-tissue clearing, were performed to monitor BSCB disruption and verify relevant injury mechanisms. Clinically applied target temperature management (TTM) to reduce the core body temperature was tested for the efficacy of attenuating BSCB disruption. RESULTS: Barrier leakage was detected in the contusion epicenter within several minutes and then gradually spread to more distant regions. Membrane expression of the main tight junction proteins remained unaltered at four hours post-injury. Many junctional gaps emerged in paracellular tight junctions at the small vessels from multiple spinal cord segments at 15 min post-injury. A previously unnoticed pathological hemodynamic change was observed in the venous system, which likely facilitated gap formation and barrier leakage by exerting abnormal physical force on the BSCB. Leukocytes were quickly initiated to transverse through the BSCB within 30 min post-SCI, actively facilitating gap formation and barrier leakage. Inducing leukocyte transmigration generated gap formation and barrier leakage. Furthermore, pharmacological alleviation of pathological hemodynamic changes or leukocyte transmigration reduced gap formation and barrier leakage. TTM had very little protective effects on the BSCB in the early period of SCI other than partially alleviating leukocyte infiltration. CONCLUSIONS: Our data show that BSCB disruption in the early period of SCI is a secondary change, which is indicated by widespread gap formation in tight junctions. Pathological hemodynamic changes and leukocyte transmigration contribute to gap formation, which could advance our understanding of BSCB disruption and provide new clues for potential treatment strategies. Ultimately, TTM is inadequate to protect the BSCB in early SCI.

The effectiveness of virtual reality, augmented reality, and mixed reality training in total hip arthroplasty: a systematic review and meta-analysis.

BACKGROUND: Extended reality (XR), including virtual reality (VR), augmented reality (AR), and mixed reality (MR), has been used in the training of total hip arthroplasty (THA). This study aims to examine the effectiveness of XR training in THA. METHODS: In this systematic review and meta-analysis, we searched PubMed (MEDLINE), EMBASE (OVID), Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and clinicaltrials.gov from inception to September 2022 for eligible studies. The Review Manager 5.4 software was applied to compare accuracy of inclination and anteversion, and surgical duration between XR training and conventional methods. RESULTS: We identified 213 articles, of which 4 randomized clinical trials and 1 prospective controlled study including 106 participants met inclusion criteria. The pooled data indicated the XR training had better accuracy of inclination and shorter surgical duration than conventional methods (MD = -2.07, 95% CI [- 4.02 to -0.11], P = 0.04; SMD = -1.30, 95% CI [- 2.01 to -0.60], P = 0.0003), but the accuracy of anteversion was similar in the two groups. CONCLUSIONS: This systematic review and meta-analysis found XR training had better accuracy of inclination and shorter surgical duration than conventional methods in THA, but the accuracy of anteversion was similar. Based on the pooled results, we suggested that XR training can better improve trainees' surgical skills than conventional methods in THA.

Dual-crosslinked network of polyacrylamide-carboxymethylcellulose hydrogel promotes osteogenic differentiation in vitro.

In our previous study, we successfully designed a dual-crosslinked network hydrogel by introducing the monomers acrylamide (AM), carboxymethylcellulose (CMC), zeolitic imidazolate framework-8 (ZIF-8), and alendronate (Aln). With the simultaneous presentation of physical and chemical crosslinks, the fabricated hydrogel with 10 % concentration of Aln@ZIF-8 (PAM-CMC-10%Aln@ZIF-8) exhibited excellent mechanical characteristics, high Aln loading efficiency (63.83 %), and a slow release period (6 d). These results demonstrate that PAM-CMC-10%Aln@ZIF-8 is a potential carrier for delaying Aln. In this study, we mainly focused on the biocompatibility and osteogenic ability of PAM-CMC-10%Aln@ZIF-8 in vitro, which is a continuation of our previous work. First, this study investigated the biocompatibility of dual-crosslinked hydrogels using calcein-AM/Propidium Iodide and cell counting kit-8. The morphology of rat bone mesenchymal stem cells was assessed using FITC-phalloidin/DAPI and vinculin immunostaining. Finally, osteogenic induction ability in vitro was assessed via alkaline phosphatase expression and alizarin red S staining, which was also confirmed using real-time PCR at the gene level and immunofluorescence at the protein level. The results indicated that the introduction of Aln enabled a dual-crosslinked hydrogel with superior biocompatibility and outstanding osteogenic differentiation ability in vitro, providing a solid foundation for subsequent animal experiments in vivo.

Moderate systemic therapeutic hypothermia is insufficient to protect blood-spinal cord barrier in spinal cord injury.

Blood-spinal cord barrier (BSCB) disruption is a pivotal event in spinal cord injury (SCI) that aggravates secondary injury but has no specific treatment. Previous reports have shown that systemic therapeutic hypothermia (TH) can protect the blood-brain barrier after brain injury. To verify whether a similar effect exists on the BSCB after SCI, moderate systemic TH at 32°C was induced for 4 h on the mice with contusion-SCI. In vivo two-photon microscopy was utilized to dynamically monitor the BSCB leakage 1 h after SCI, combined with immunohistochemistry to detect BSCB leakage at 1 and 4 h after SCI. The BSCB leakage was not different between the normothermia (NT) and TH groups at both the in vivo and postmortem levels. The expression of endothelial tight junctions was not significantly different between the NT and TH groups 4 h after SCI, as detected by capillary western blotting. The structural damage of the BSCB was examined with immunofluorescence, but the occurrence of junctional gaps was not changed by TH 4 h after SCI. Our results have shown that moderate systemic TH induced for 4 h does not have a protective effect on the disrupted BSCB in early SCI. This treatment method has a low value and is not recommended for BSCB disruption therapy in early SCI.

The Glial Cells Respond to Spinal Cord Injury.

It is been over 100 years since glial cells were discovered by Virchow. Since then, a great deal of research was carried out to specify these further roles and properties of glial cells in central nervous system (CNS). As it is well-known that glial cells, such as astrocytes, microglia, oligodendrocytes (OLs), and oligodendrocyte progenitor cells (OPCs) play an important role in supporting and enabling the effective nervous system function in CNS. After spinal cord injury (SCI), these glial cells play different roles in SCI and repair. In this review, we will discuss in detail about the role of glial cells in the healthy CNS and how they respond to SCI.

Antibacterial biomaterials in bone tissue engineering.

Bone infection is a devastating disease characterized by recurrence, drug-resistance, and high morbidity, that has prompted clinicians and scientists to develop novel approaches to combat it. Currently, although numerous biomaterials that possess excellent biocompatibility, biodegradability, porosity, and mechanical strength have been developed, their lack of effective antibacterial ability substantially limits bone-defect treatment efficacy. There is, accordingly, a pressing need to design antibacterial biomaterials for effective bone-infection prevention and treatment. This review focuses on antibacterial biomaterials and strategies; it presents recently reported biomaterials, including antibacterial implants, antibacterial scaffolds, antibacterial hydrogels, and antibacterial bone cement types, and aims to provide an overview of these antibacterial materials for application in biomedicine. The antibacterial mechanisms of these materials are discussed as well.

Persistent oppression and simple decompression both exacerbate spinal cord ascorbate levels.

Background: Surgical decompression after acute spinal cord injury has become the consensus of orthopaedic surgeons. However, the choice of surgical decompression time window after acute spinal cord injury has been one of the most controversial topics in orthopaedics. Objective: We apply an online electrochemical system (OECS) for continuously monitoring the ascorbate of the rats' spinal cord to determine the extent to which ascorbate levels were influenced by contusion or sustained compression. Methods: Adult Sprague-Dawley rats (n=10) were instrumented for ascorbate concentration recording and received T11 drop spinal cord injury (SCI). The Group A (n=5) were treated with immediately decompression after SCI. The Group B (n=5) were contused and oppressed until 1 h after the injury to decompress. Results: The ascorbate level of spinal cord increased immediately by contusion injury and reached to 1.62 µmol/L ± 0.61 µmol/L (217.30% ± 95.09% of the basal level) at the time point of 60 min after the injury. Compared with the Group A, the ascorbate level in Group B increased more significantly at 1 h after the injury, reaching to 3.76 µmol/L ± 1.75 µmol/L (430.25% ± 101.30% of the basal level). Meanwhile, we also found that the decompression after 1 hour of continuous compression will cause delayed peaks of ascorbate reaching to 5.71 µmol/L ± 2.69 µmol/L (627.73% ± 188.11% of the basal level). Conclusion: Our study provides first-hand direct experimental evidence indicating ascorbate is directly involved in secondary spinal cord injury and exhibits the dynamic time course of microenvironment changes after continuous compression injury of the spinal cord.

Bioactive Pore-Forming Bone Adhesives Facilitating Cell Ingrowth for Fracture Healing.

The effectiveness of commercial bone adhesives is known to be hampered by the weak efficacy of cell ingrowth. The strategy of macropore-forming, especially bioactive macropores, holds considerable promise to circumvent this problem, thereby promoting fracture healing. Herein, a class of bioactive glass-involved macropore-embedded bone adhesives is developed, which is capable of facilitating the migration of bone-derived mesenchymal stromal cells into the adhesive layer and differentiation into osteocytes. The integration of bioactive glass-particle-encapsulated porogens in the bone adhesives is key to this approach. A robust instant bonding on the bone adhesive and a high efficiency of bone regeneration on a mouse skull are observed, both of which are vital for clinical applications and personalized surgical procedures. This work represents a general strategy to design biomaterials with high cell-ingrowth efficacy.

Therapeutic hypothermia effectively reduces elevated extracellular ascorbate concentrations caused by acute spinal cord injury.

In recent years, systemic hypothermia has taken the spotlight for its use in spinal cord injury (SCI) research fields, but detailed molecular mechanisms are still not fully understood. In this study, we use an online-electrochemical system (OECS) to in vivo continuously monitor the ascorbate of the rats' spinal cord. We find that the basal level of ascorbate in rat spinal cord is 1.85 ± 0.88 µmol L-1 (n = 20). It increased immediately after SCI and reached 2.36 ± 0.65 µmol L-1 (164.90% ± 7.99% of the basal level) (n = 5) at 60 min after the injury. The SCI-induced extracellular ascorbate increase is obviously attenuated by therapeutic hypothermia (28 °C) after injury and ascorbate returns to 3.01 ± 0.59 µmol L-1 (100.24% ± 5.02% of the basal level) (n = 5), at 60 min after SCI. These results substantially manifest that the OECS for ascorbate detection could be employed as a platform for understanding the pathological changes during spinal cord injury. This study provides experimental evidence for the essential roles of ascorbate in SCI which could serve as a biomarker for SCI. Our findings also raise the possibility that therapeutic hypothermia can effectively exert neuroprotection in the acute phase of SCI.

Radiotherapy Suppresses Bone Cancer Pain through Inhibiting Activation of cAMP Signaling in Rat Dorsal Root Ganglion and Spinal Cord.

Radiotherapy is one of the major clinical approaches for treatment of bone cancer pain. Activation of cAMP-PKA signaling pathway plays important roles in bone cancer pain. Here, we examined the effects of radiotherapy on bone cancer pain and accompanying abnormal activation of cAMP-PKA signaling. Female Sprague-Dawley rats were used and received tumor cell implantation (TCI) in rat tibia (TCI cancer pain model). Some of the rats that previously received TCI treatment were treated with X-ray radiation (radiotherapy). Thermal hyperalgesia and mechanical allodynia were measured and used for evaluating level of pain caused by TCI treatment. PKA mRNA expression in dorsal root ganglion (DRG) was detected by RT-PCR. Concentrations of cAMP, IL-1ß, and TNF-α as well as PKA activity in DRG and the spinal cord were measured by ELISA. The results showed that radiotherapy significantly suppressed TCI-induced thermal hyperalgesia and mechanical allodynia. The level of PKA mRNA in DRG, cAMP concentration and PKA activity in DRG and in the spinal cord, and concentrations of IL-1ß and TNF-α in the spinal cord were significantly reduced by radiotherapy. In addition, radiotherapy also reduced TCI-induced bone loss. These findings suggest that radiotherapy may suppress bone cancer pain through inhibition of activation of cAMP-PKA signaling pathway in DRG and the spinal cord.